Cytokine Gene Polymorphisms in Infectious and Inflammatory Diseases

  • P. Stokkers
  • L. Camoglio
  • S. J. H. van Deventer
Conference paper
Part of the Yearbook of Intensive Care and Emergency Medicine book series (YEARBOOK, volume 1996)

Abstract

Infectious and inflammatory diseases are characterized by local generation of inflammatory mediators, and recruitment of inflammatory cells from the circulation into local tissues. These processes are tightly regulated by the cytokines that are produced by lymphocytes and macrophages. Cytokines induce a wide range of secondary mediators, including other cytokines, and interact with various cells in an endocrine, paracrine or autocrine manner. The inflammatory processes that result from infectious and non-infectious stimuli are usually initially related to the severity of the pro-inflammatory stimulus, but at later stages may become dependent on the balance of the production of pro- and anti-inflammatory mediators. Defects in the control of inflammation in part explain the observation that relatively minor injury may cause extensive tissue damage, such as may occur in sepsis and certain autoimmune diseases, and the regulation of cytokine production may be a key factor in the perpetuation of inflammation. The transcription rate of most cytokine genes is strictly regulated, and the production of some cytokines is additionally restricted by translational- and posttranslational control mechanisms. In recent years it has become apparent that cytokine genes are polymorphic, and the presence of certain alleles may correlate with enhanced or reduced cytokine production. Although it has been demonstrated that in some instances such a relationship was directly caused by altered binding of DNA-binding proteins (transcription factors) that regulate transcription, in many cases the precise connection of cytokine gene polymorphisms with the production of specific cytokines on the one hand, and disease severity on the other hand remains uncertain.

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Refrences

  1. 1.
    Nedwin GE, Naylor SL, Sakaguchi AY, et al (1985) Human tumor necrosis factor genes: Structure, homology and chromosomal localization. Nucl Acid Res 13: 6361–6373CrossRefGoogle Scholar
  2. 2.
    Nedospasov SA, Shakov AN, Turetskaya RL, et al (1986) Tandem arrangement of the genes coding for human tumor necrosis factor (TNF-α) and lymphotoxin (TNF-β) in human genome. Cold Spring Harbor Symp Quant Biol 51 : 611–625PubMedGoogle Scholar
  3. 3.
    Spies T, Morton CC, Nedospasov SA, Fiers W, Pious D, Strominger JL (1986) Genes for the tumor necrosis factor-α and β are linked to the human major histocompability complex. Proc Natl Acad Sci USA 83: 8699–8702PubMedCrossRefGoogle Scholar
  4. 4.
    Carroll MC, Katzman P, Alicot EM, et al (1987) Linkage map of the human major histocompatibliy complex including the tumor necrosis factor genes. Proc Natl Acad Sci USA 84: 8535–8539PubMedCrossRefGoogle Scholar
  5. 5.
    Dunham I, Sargent CA, Trowsdale J, Campbell D (1987) Molecular mapping of the human major histocompatibility complex by puIs-field electrophoresis. Proc Natl Acad Sci USA 84: 7237–7241PubMedCrossRefGoogle Scholar
  6. 6.
    Partanen J, Koskimies S (1988) Low degree of DNA polymorphisms in the HLA-linked lymphotoxin (tumour necrosis factor β) gene. Scand J Immunol 28: 313–316PubMedCrossRefGoogle Scholar
  7. 7.
    Webb GC, Chaplin DD (1990) Genetic variability at the human tumor necrosis factor loci. J Immunol 145: 1278–1285PubMedGoogle Scholar
  8. 8.
    Fugger L, Morling N, Ryder LP, et al (1989) Ncol restriction fragment length polymorphism (RFLP) of the tumor necrosis factor (TNFα) region in primary biliary sclerosis and in healthy Danes. Scand J Immunol 30: 185–189PubMedCrossRefGoogle Scholar
  9. 9.
    Nedospasov SA, Udalova IA, Kuprash DV, Turetskaya RL (1991) DNA sequence polymorphism at the human tumor necrosis factor (TNF) locus. J Immunology 147: 1053–1059Google Scholar
  10. 10.
    Jongeneel CV, Briant L, Udalova IA, Sevin A, Nedospasov SA, Cambon-Thomsen A (1991) Extensive genetic polymorphism in the human tumor necrosis factor region and relation to extended HLA haplotypes. Proc Natl Acad Sci USA 88: 9717–9721PubMedCrossRefGoogle Scholar
  11. 11.
    Udalova IA, Nedospasov SA, Webb GC, Chaplin DD, Turestkaya RL (1993) Highly informative typing of the human TNF locus using six adjacent polymorphic markers. Genomics 16: 180–186PubMedCrossRefGoogle Scholar
  12. 12.
    Messer G, Spengler U, Jung MC, et al (1991) Polymorphic structure of the tumor necrosis factor (TNF) locus: an Ncol polymorphism in the first intron of the human TNF-β gene correlates with a variant amino acid in position 26 and a reduced level of TNF-β production. J Exp Med 173: 209–219PubMedCrossRefGoogle Scholar
  13. 13.
    Pociot F, Mølvig J, Wogensen L, et al (1991) A tumor necrosis factor beta gene polymorphism in relation to monokine secretion and insulin-dependent diabetes mellitus. Scand J Immunol 33: 37–49PubMedCrossRefGoogle Scholar
  14. 14.
    Choo SY, Spies T, Strominger JL, Hansen J (1988) Polymorphism in the tumor necrosis factor gene: Association with HLA-B and DR haplotypes. Hum Immunol 23: 86CrossRefGoogle Scholar
  15. 15.
    Badenhoop K, Schwarz G, Trowsdale J, Lewis V, Gale EAM, Botazzo GF (1989) TNF-α gene polymorphisms in type 1 diabetes mellitus. Diabetologia 32: 445–448PubMedCrossRefGoogle Scholar
  16. 16.
    Dawkins RL, Leaver A, Cameron PU, Martin E, Kay PH, Christiansen FT (1989) Some disease-associated ancestral haplotypes carry a polymorphism of TNF. Hum Immunol 26: 91–97PubMedCrossRefGoogle Scholar
  17. 17.
    Tiwari JI (1985) HLA and disease associations. Springer Verlag, Berlin, pp 32–48CrossRefGoogle Scholar
  18. 18.
    Derkx HHF, Bruin KF, Jongeneel CV, et al (1995) Familial differences in endotoxininduced TNF release in whole blood and peripheral blood mononuclear cells in vitro. Relationship to TNF gene polymorphism. J Endotox Res 2: 19–25Google Scholar
  19. 19.
    Fugger L, Bendtzen L, Morling N, Ryder L, Svejgaard A (1989) Possible correlation of TNFα-production with RFLP in humans. Eur J Haematol 43: 255–254PubMedCrossRefGoogle Scholar
  20. 20.
    Sachs JA, Whichelow CE, Hitman GA, Niven M, Thode H, Meager A (1990) The effect of HLA and insulin-dependent diabetes mellitus on the secretion levels of tumor necrosis factor alpha and beta and gamma interferon. Scand J Immunol 32: 703–708PubMedCrossRefGoogle Scholar
  21. 21.
    Pociot F, Briant L, Jongeneel CV (1993) Association of tumor necrosis factor (TNF) and class II major histocompatibility complex alleles with secretion of TNF alpha and beta by human mononuclear cells: A possible link to insulin-dependent diabetes mellitus. Eur J Immunol 23: 224–231PubMedCrossRefGoogle Scholar
  22. 22.
    Santamaria P, Gehrz RC, Bryan MK, Barbosa JJ (1989) Involvement of class II MHC molecules in the LPS-induction of IL-1/TNF secretions by human monocytes. J Immunol 143: 913–922PubMedGoogle Scholar
  23. 23.
    Toungouz M, Denys CH, Andrien ME, De Groote D, Dupont EC (1994) Tumor necrosis factor-α and interleukin-6 production by variations of DR4 polymorphism during the primary mixed lymphocyte reaction. Transplantation 58: 1393–1398PubMedGoogle Scholar
  24. 24.
    Wilson AG, Di Giovine FS, Blakemore AIF, Duff GW (1992) Single base polymorphism in the human tumor necrosis factor alfa (TNF-α) gene detectable by Ncol restriction of PCR product. Hum Mol Genet 1: 353PubMedCrossRefGoogle Scholar
  25. 25.
    Wilson AG, De Vries N, Pociot F, di Giovine FS, Van der Putte LBA, Duff GW (1993) An allelic polymorphism within the tumor necrosis factor a promotor is strongly associated with HLA AI, B8, and DR 3 alleles. J Exp Med 177: 557–560PubMedCrossRefGoogle Scholar
  26. 26.
    Wilson AG, Symons JA, McDowell TL, di Giovine FS, Duff GW (1994) Effects of tumor necrosis (TNF-a) promotor base transition on transcriptional activity. Br J Rheumatol 33 : 89 (Abst)CrossRefGoogle Scholar
  27. 27.
    Abraham LJ, French MAH, Dawkins RL (1993) Polymorphic MHC ancestral haplotypes affect the activity of tumor necrosis factor-α. Clin Exp Immunol 92: 14–18PubMedCrossRefGoogle Scholar
  28. 28.
    D’Alfonso S, Richiardi PM (1994) A polymorphic variation in a putative regulation box of the TNFa promotor region. Immunogenet 39: 150–154Google Scholar
  29. 29.
    Pociot F, D’ Alfonso S, Compasso S, Scorza R, Richiardi PM (1995) Functional analysis of a new polymorphism in the human TNF-α gene promotor. Scand J Immunol 42: 501–504PubMedCrossRefGoogle Scholar
  30. 30.
    Brinkman BMN, Kaijzel EL, Huizinga TWJ, Giphart MJ, Breedveld FC, Verweij CL (1995) Detection of a C-insertion polymorphism within the human tumor necrosis factor alpha (TNFα) gene. Hum Genet 96: 493PubMedCrossRefGoogle Scholar
  31. 31.
    Webb AC, Collins KL, Auron PE, et al (1986) Interleukin-1 gene (IL-1) assigned to the long arm of human chromosome 2. Lymphokine Res 5: 77–85PubMedGoogle Scholar
  32. 32.
    Modi WS, Masuda A, Yamada M, et al (1988) Chromosomal localization of the human interleukin-1a gene. Genomics 2: 310–314PubMedCrossRefGoogle Scholar
  33. 33.
    Lafage M, Maroc N, Dubreuil P, et al (1989) The human interleukin-1α gene is located on the long arm of chromosome 2 at band q 13. Blood 73: 104–107PubMedGoogle Scholar
  34. 34.
    Steinkasser A, Spurr NK, Cox S, Jeggo P, Sim RB (1992) The human IL-1 receptor antagonist gene (IL-1ra) maps to chromosome 2q14-q21 in the region of the IL-1α and IL-1β loci. Genomics 13: 654–657CrossRefGoogle Scholar
  35. 35.
    Patterson D, Jones C., Hart I, et al (1993) The human interleukin-1 receptor antagonist (IUra) gene is located in the chromosome 2q14 region. Genomics 15: 173–176PubMedCrossRefGoogle Scholar
  36. 36.
    Lennard A, Gorman P, Carrier M, et al (1993) Cloning and chromosome mapping of the interleukin-1 receptor antagonist gene. Cytokine 4: 83–89CrossRefGoogle Scholar
  37. 37.
    Nicklin JH, Weith A, Duff GW (1993) A physical map of the region encompassing the human interleukin-1α, interleukin-1β, and interleukin receptor antagonist genes. Genomics 19: 382–384CrossRefGoogle Scholar
  38. 38.
    Furutani Y, Notake M, Fukui T, et al (1986) Complete nucleotide sequence of the gene for human interleukin alpha. Nucleic Acids Res 14: 3167–3179PubMedCrossRefGoogle Scholar
  39. 39.
    Bailly S, di Giovine FS, Duff GW (1993) Polymorphic tandem repeat region in interleukin- lα intron 6. Hum Genet 91: 85–86PubMedCrossRefGoogle Scholar
  40. 40.
    Bailly S, di Giovine FS, Blakemore AIF, Duff GW (1993) Genetic polymorphism of human interleukin-1α. Eur J Immunol 23: 1240–1245PubMedCrossRefGoogle Scholar
  41. 41.
    v/d Velden PA, Reitsma PH (1993) Amino acid dimorphism in IL-1α is detectable by PCR amplification. Hum Mol Genet 2: 1753PubMedCrossRefGoogle Scholar
  42. 42.
    Todd S, Naylor SL (1991) Dinucleotide repeat polymorphism in the human interleukin 1 alpha gene (IL-1α) Nucl Acid Res 19: 3756Google Scholar
  43. 43.
    McDowell TL, Symons JA, Ploski R, Førre Ø, Duff GW (1993) A polymorphism in the region of the interleukin-1 alpha gene is associated with juvenile chronic arthritis. Br J Rheumatol 32 (Suppl 1): 162 (Abst)CrossRefGoogle Scholar
  44. 44.
    di Giovine FS, Takhsh E, Blakemore AIF, Duff GW (1992) Single base polymorphism at-511 in the human interleukin-1β gene (IL-1β). Human Mol Genet 1: 450CrossRefGoogle Scholar
  45. 45.
    Steinkasserer A, Koeble K, Sim RB (1991) Length variation within intron 2 of the human IL-1 receptor antagonist protein gene. Nucleic Acids Res 19: 5095PubMedCrossRefGoogle Scholar
  46. 46.
    Tarlow JK, Blakemore AIF, Lennard A, et al (1993) Polymorphism in human receptor antagonist gene intron 2 is caused by variable number of an 86-bp tandem repeat. Hum Genet 91 : 403–404PubMedCrossRefGoogle Scholar
  47. 47.
    Danis VA, Millington M, Hyland VJ, Grennan D (1995) Cytokine production by normal human monocytes: Inter-subject variation and relationship to an IL-1 receptor antagonist (IL-1ra) gene polymorphism. Clin Exp Immunol 99: 303–310PubMedCrossRefGoogle Scholar
  48. 48.
    McLeod R, Bushman E, Arbuckle LD, Skamene (1995) Immunogenetics in the analysis of resistance to intracellular pathogens. Curr Opin Immunol 7: 539–552PubMedCrossRefGoogle Scholar
  49. 49.
    Grau GE, Taylor TE, Molyneux ME (1989) Tumor necrosis factor and disease severity in children with falciparum malaria. N Engl J Med 320: 1586–1591PubMedCrossRefGoogle Scholar
  50. 50.
    Kwiatkowski D, Hill AV, Sanbou I, et al (1990) TNF concentration in fatal cerebral, non-fatal cerebral, and uncomplicated Plasmodium falciparum malaria. Lancet 336: 1201–1204PubMedCrossRefGoogle Scholar
  51. 51.
    Castes M, Trujillo D, Rojas ME, et al (1993) Serum levels of tumor necrosis factor in patients with American cutaneous Leishmaniasis. Biol Res 26: 233–238PubMedGoogle Scholar
  52. 52.
    Berendt AR, Simmons DL, Transey J, Newbold CI, Marsh K (1989) Intercellular adhesion molecule-l is an endothelial cell adhesion receptor for Plasmodium falciparum. Nature 341 : 57–59PubMedCrossRefGoogle Scholar
  53. 53.
    McGuire W, Hill AVS, Allsopp CEM, Greenwood BM, Kwiatkowski D (1994) Variation in the TNF-α promotor region associated with susceptibility to cerebral malaria. Nature 371 : 508–511PubMedCrossRefGoogle Scholar
  54. 54.
    Cabrera M, Shaw MA, Sharples C, Williams H, Castes M, Convit J, Blackwell JM (1995) Polymorphism in tumor necrosis factor genes associated with mucocutaneous Leishmaniasis. J Exp Med 182: 1259–1264PubMedCrossRefGoogle Scholar
  55. 55.
    Vincek V, Kurimoto I, Streilein JW (1994) Polymorphism at the tumor necrosis factor-a and susceptibility to toxoplasmic encephalitis, ultraviolet B-induced immune impairment and mouse AIDS. J Acq Imm Def Syn 7: 734–739Google Scholar
  56. 56.
    Freund YR, Chaim GS, Jacob CO, Suzuki Y, Remington JS (1992) Polymorphisms in the tumor necrosis factor-α (TNF-α) mRNA in infected brain tissue. J Exp Med 175: 683–688PubMedCrossRefGoogle Scholar
  57. 57.
    Clay FE, Cork MJ, Tarlow JK, et al (1994) Interleukin-1 receptor antagonist gene polymorphism association with lichen sclerous. Hum Genet 94: 407–410PubMedCrossRefGoogle Scholar
  58. 58.
    Blakemore AIF, Tarlow JK, Cork MJ, Gordon C, Emery P, Duff GW (1994) Interleukin-1 receptor antagonist gene polymorphism as a disease severity factor in systemic lupus erythematosus. Arthr Rheum 9: 1380–1385CrossRefGoogle Scholar
  59. 59.
    Cork MJ, Tarlow JK, Clay FE, et al (1995) An allele of the interleukin-1 receptor antagonist as a genetic severity factor in alopecia areata. J Invest Dermatol 104: 15S-16SPubMedGoogle Scholar
  60. 60.
    Mansfield JC, Holden H, Tadow J, et al (1994) Novel genetic association between ulcerative colitis and the anti-inflammatory cytokine interleukin-1 antagonist. Gastroenterology 106: 637–642PubMedGoogle Scholar
  61. 61.
    Isaacs KL, Sartor RB, Haskill S (1992) Cytokine messenger RNA profIles in inflammatory bowel disease mucosa detected by polymerase chain reaction amplification. Gastroentrol 103: 1587–1595Google Scholar
  62. 62.
    Wilson WG, Duff GW (1995) Genetic traits in common disease support the adage that autoimmunity is the price paid for eradication of infectious disease. Br Med J 310: 1482–1483CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1996

Authors and Affiliations

  • P. Stokkers
  • L. Camoglio
  • S. J. H. van Deventer

There are no affiliations available

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